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ERK1/2 signaling dominates over RhoA signaling in regulating early changes in RNA expression induced by endothelin-1 in neonatal rat cardiomyocytes
Cardiomyocyte hypertrophy is associated with changes in gene expression. Extracellular signal-regulated kinases 1/2 (ERK1/2) and RhoA [activated by hypertrophic agonists (e.g. endothelin-1)] regulate gene expression and are implicated in the response, but their relative significance in regulating the cardiomyocyte transcriptome is unknown. Our aim was to establish the significance of ERK1/2 and/or RhoA in the early cardiomyocyte transcriptomic response to endothelin-1.Cardiomyocytes were exposed to endothelin-1 (1 h) with/without PD184352 (to inhibit ERK1/2) or C3 transferase (C3T, to inhibit RhoA). RNA expression was analyzed using microarrays and qPCR. ERK1/2 signaling positively regulated approximately 65% of the early gene expression response to ET-1 with a small (approximately 2%) negative effect, whereas RhoA signaling positively regulated approximately 10% of the early gene expression response to ET-1 with a greater (approximately 14%) negative contribution. Of RNAs non-responsive to endothelin-1, 66 or 448 were regulated by PD184352 or C3T, respectively, indicating that RhoA had a more significant effect on baseline RNA expression. mRNAs upregulated by endothelin-1 encoded a number of receptor ligands (e.g. Ereg, Areg, Hbegf) and transcription factors (e.g. Abra/Srf) that potentially propagate the response.ERK1/2 dominates over RhoA in the early transcriptomic response to endothelin-1. RhoA plays a major role in maintaining baseline RNA expression but, with upregulation of Abra/Srf by endothelin-1, RhoA may regulate changes in RNA expression over longer times. Our data identify ERK1/2 as a more significant node than RhoA in regulating the early stages of cardiomyocyte hypertrophy
Scalar and vector Slepian functions, spherical signal estimation and spectral analysis
It is a well-known fact that mathematical functions that are timelimited (or
spacelimited) cannot be simultaneously bandlimited (in frequency). Yet the
finite precision of measurement and computation unavoidably bandlimits our
observation and modeling scientific data, and we often only have access to, or
are only interested in, a study area that is temporally or spatially bounded.
In the geosciences we may be interested in spectrally modeling a time series
defined only on a certain interval, or we may want to characterize a specific
geographical area observed using an effectively bandlimited measurement device.
It is clear that analyzing and representing scientific data of this kind will
be facilitated if a basis of functions can be found that are "spatiospectrally"
concentrated, i.e. "localized" in both domains at the same time. Here, we give
a theoretical overview of one particular approach to this "concentration"
problem, as originally proposed for time series by Slepian and coworkers, in
the 1960s. We show how this framework leads to practical algorithms and
statistically performant methods for the analysis of signals and their power
spectra in one and two dimensions, and, particularly for applications in the
geosciences, for scalar and vectorial signals defined on the surface of a unit
sphere.Comment: Submitted to the 2nd Edition of the Handbook of Geomathematics,
edited by Willi Freeden, Zuhair M. Nashed and Thomas Sonar, and to be
published by Springer Verlag. This is a slightly modified but expanded
version of the paper arxiv:0909.5368 that appeared in the 1st Edition of the
Handbook, when it was called: Slepian functions and their use in signal
estimation and spectral analysi
Seeing is believing: the nocturnal malarial mosquito Anopheles coluzzii responds to visual host-cues when odour indicates a host is nearby
Background: The immediate aim of our study was to analyse the behaviour of the malarial mosquito Anopheles coluzzii (An. gambiae species complex) near a human host with the ultimate aim of contributing to our fundamental understanding of mosquito host-seeking behaviour and the overall aim of identifying behaviours that could be exploited to enhance sampling and control strategies.
Results: Based on 3D video recordings of individual host-seeking females in a laboratory wind-tunnel, we found that despite being a nocturnal species, An. coluzzii is highly responsive to a visually conspicuous object, but only in the presence of host-odour. Female mosquitoes approached and abruptly veered away from a dark object, which suggests attraction to visual cues plays a role in bringing mosquitoes to the source of host odour. It is worth noting that the majority of our recorded flight tracks consisted of highly stereotyped âdippingâ sequences near the ground, which have been mentioned in the literature, but never before quantified.
Conclusions: Our quantitative analysis of female mosquito flight patterns within ~1.5 m of a host has revealed highly relevant information about responsiveness to visual objects and flight height that could revolutionise the efficacy of sampling traps; the capturing device of a trap should be visually conspicuous and positioned near the ground where the density of host-seeking mosquitoes would be greatest. These characteristics are not universally present in current traps for malarial mosquitoes. The characterisation of a new type of flight pattern that is prevalent in mosquitoes suggests that there is still much that is not fully understood about mosquito flight behaviour
Authorship trends in software engineering
This paper aims to examine authorship trends in software engineering, especially those related to the number of authors, of scientific publications. We collected and mined around 70.000 entries from DBLP for 122 conferences and journals, for the period 1971â2012, in order to process several bibliometric indicators. We provide evidence that the number of authors of articles in software engineering is increasing on average around +0.40 authors/decade. The results also indicate that until 1980, the majority of the articles have a sole author, while nowadays articles with 3 or 4 authors represent almost half of the total.Fundação para a CiĂȘncia e a Tecnologia (FCT
Population Empirical Likelihood Estimation in Dual Frame Surveys
Dual frame surveys are a device to reduce the costs derived from data
collection in surveys and improve coverage for the whole target population. Since
their introduction, in the 1960âs, dual frame surveys have gained much attention
and several estimators have been formulated based on a number of different approaches. In this work, we propose new dual frame estimators based on the population empirical likelihood method originally proposed by Chen and Kim (2014) and
using both the dual and the single frame approach. The extension of the proposed
methodology to more than two frame surveys is also sketched. The performance
of the proposed estimators in terms of relative bias and relative mean squared
error is tested through simulation experiments. These experiments indicate that
the proposed estimators yield better results than other likelihood-based estimators
proposed in the literature.Ministerio de EconomĂa y Competitividad of Spai
One-Loop Calculation of the Oblique S Parameter in Higgsless Electroweak Models
We present a one-loop calculation of the oblique S parameter within Higgsless
models of electroweak symmetry breaking and analyze the phenomenological
implications of the available electroweak precision data. We use the most
general effective Lagrangian with at most two derivatives, implementing the
chiral symmetry breaking SU(2)_L x SU(2)_R -> SU(2)_{L+R} with Goldstones,
gauge bosons and one multiplet of vector and axial-vector massive resonance
states. Using the dispersive representation of Peskin and Takeuchi and imposing
the short-distance constraints dictated by the operator product expansion, we
obtain S at the NLO in terms of a few resonance parameters. In
asymptotically-free gauge theories, the final result only depends on the
vector-resonance mass and requires M_V > 1.8 TeV (3.8 TeV) to satisfy the
experimental limits at the 3 \sigma (1\sigma) level; the axial state is always
heavier, we obtain M_A > 2.5 TeV (6.6 TeV) at 3\sigma (1\sigma). In
strongly-coupled models, such as walking or conformal technicolour, where the
second Weinberg sum rule does not apply, the vector and axial couplings are not
determined by the short-distance constraints; but one can still derive a lower
bound on S, provided the hierarchy M_V < M_A remains valid. Even in this less
constrained situation, we find that in order to satisfy the experimental limits
at 3\sigma one needs M_{V,A} > 1.8 TeV.Comment: 34 pages, 9 figures. Version published in JHEP. Some references and
sentences have been added to facilitate the discussio
"A few good men": Public sector audit in the Swan River Colony, 1828-1835
The appointment of the Auditor General to undertake public sector audit is the primary instrument used to safeguard public finances in most contemporary Westminster-based democracies. It is axiomatic that the independence of the Auditor General from executive government is a critical element in ensuring the effectiveness of the role, yet this separation is a relatively recent phenomenon. Those responsible for nineteenth century public sector audit in the Australian colonies operated in what would today be considered an unacceptable environment, with little, if any, independence from the executive arm of government. Yet, while several other Australian colonies suffered from the mismanagement of government finances, there is nothing to show that the Swan River Colony experienced much more than clerical errors and minor administrative oversights. In this article, we explore the extent to which satisfactory public financial management in the Swan River Colony occurred as a result of both good financial management systems (in the context of the era) and the appointment of competent and ethical administrators â âa few good menâ
Trend-TDT â a transmission/disequilibrium based association test on functional mini/microsatellites
<p>Abstract</p> <p>Background</p> <p>Minisatellites and microsatellites are associated with human disease, not only as markers of risk but also involved directly in disease pathogenesis. They may play significant roles in replication, repair and mutation of DNA, regulation of gene transcription and protein structure alteration. Phenotypes can thus be affected by mini/microsatellites in a manner proportional to the length of the allele. Here we propose a new method to assess the linear trend toward transmission of shorter or longer alleles from heterozygote parents to affected child.</p> <p>Results</p> <p>This test (trend-TDT) performs better than other TDT (Transmission/Disequilibrium Test) type tests, such as TDT<sub>max </sub>and TDT<sub>L/S</sub>, under most marker-disease association models.</p> <p>Conclusion</p> <p>The trend-TDT test is a more powerful association test when there is a biological basis to suspect a relationship between allele length and disease risk.</p
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